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The first real major breakthrough that laid the basis of HLA antibody detection in the field of solid organ transplantation, came with the introduction of the complement dependent cytotoxicity (CDC) test in 1964 by Terasaki and McClelland. Since then, methods for antibody detection have evolved remarkably from conventional cell-based assays to the current advanced solid phase systems on the Luminex platform, with increasing degree of sensitivity and specificity. The latter have been indispensable for more accurate identification of donor specific HLA antibodies in broadly reactive allo antisera, and to guide donor selection and kidney paired exchange programs through virtual crossmatching, in addition to serving as excellent tools for initiating pre-transplant desensitization and post- transplant antibody monitoring. Consensus is evolving on the optimal routine employment of these methods in donor selection strategies along with an understanding of the clinical relevance of antibodies detected by each of them. The immunoassays based on the Luminex platform and flow cytometric beads are however unable to discriminate complement fixing from non-complement fixing HLA antibodies. This is important because the former are considered clinically more pertinent in the peri-transplant period. The C1q assay which is a modification of the solid phase assay based on Luminex single antigen beads, which can be used effectively to monitor high dose IVIG desensitization is essentially a surrogate complement fixing assay, retaining the exquisite sensitivity and specificity of the Luminex platform. Currently, information obtained from these assays is preliminary and much needs to be done to standardize technologies and set a consensus ‘MFI cut off’ for antibody positivity. Besides the overriding influence of anti-HLA antibodies on overall solid organ graft survival, immune response to non-HLA antigens has become a topic of substantial interest in recent years. An ever expanding list of non-HLA antigens has been implicated in graft rejection for various organs, of which the most noted are the Major Histocompatibility Complex class I chain-related molecule A (MICA), Vimentin, Myosin, Angiotensin II type 1 receptor (AT1R), Tubulin and Collagen. MICA is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in renal transplantation. Although there are clear indications of MICA antibodies being associated with adverse graft outcome, to date a definitive consensus on this relationship has not been agreed. Because MICA molecules are not expressed constitutively on immunocompetent cells such as T and B lymphocytes, it is of utmost importance to address the impact of MICA donor specific antibodies (DSA) as compared to those that are non- donor specific (NDSA) on graft outcome. The soluble isoform of MICA molecule (sMICA) that is derived from the proteolytic shedding of membrane bound molecules has the potential to engage the NK-cell activating receptor NKG2D and down-regulate its expression. Consequent to the interaction of NKG2D by sMICA, the receptor ligand complex is endocytosed and degraded and thus suppresses NKG2D mediated lysis of the target by NK cells. Thus interaction between NKG2D and sMICA leads to expansion of immunosuppressive/anergic T cells thereby resulting in suppression of NKG2D mediated host innate immunity. These concept support the possible involvement of an immunosuppressive role for sMICA during allotransplantation as shown recently for heart transplantation. This research topic focusses on the clinical utility of investigating the complete antibody repertoire in solid organ transplantation.
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Pathophysiology is the convergence of pathology (the discipline of observed changes in a diseased state) with physiology (the mechanisms of systems operation). It represents the functional changes that occur because of injury or disease. This volume provides state-of-the-art up-to-date literature reviews on pathophysiological processes in a number of disease states. The book is organised methodically in a head-to-toe systems approach examining aspects of neuropathophysiology, endocrine pathophysiology, structural biology, renal pathophysiology and genitourinary pathophysiology. This short volume on pathophysiology is intended for general medical and biomedical students at both undergraduate and postgraduate levels. In addition, it is a useful short update of recent advances in research and translational biology to those working in academia or healthcare science.
Clinical Molecular Medicine: Principles and Practice presents the latest scientific advances in molecular and cellular biology, including the development of new and effective drug and biological therapies and diagnostic methods. The book provides medical and biomedical students and researchers with a clear and clinically relevant understanding on the molecular basis of human disease. With an increased focus on new practice concepts, such as stratified, personalized and precision medicine, this book is a valuable and much-needed resource that unites the core principles of molecular biology with the latest and most promising genomic advances. Illustrates the fundamental principles and therapeutic applications of molecular and cellular biology Offers a clinically focused account of molecular heterogeneity Includes comprehensive coverage of many different disorders, including growth and development, cardiovascular, metabolic, skin, blood, digestive, inflammatory, neuropsychiatric disorders, and many more
Proceedings of the 25th Conference on Transplantation and Clinical Immunology 24--26 May 1993
Chronic graft versus host disease (GVHD) is the most common complication of allogenic bone marrow transplantation. Because of the protracted clinical course of chronic GVHD, transplant centers and hematology/oncology offices are inadequately equipped to manage these immuno-incompetent patients with a multi-system disorder. Practitioners need to be able to recognize and effectively manage chronic GVHD as a late effect of more than half of allogenic transplantations. The text is oriented for the clinician, with chapters covering staging, organ site and system-specific manifestations, treatment options, and supportive care. Drs Georgia B. Vogelsang and Steven Z. Pavletic have been pioneers in the recognition of the multi-organ complexity of this disease and have gathered the input of a variety of subspecialist physicians for this book. This book fills the gap in practical literature on chronic GVHD, providing a comprehensive, up-to-date, and clinically relevant resource for anyone who deals with cancer patients post-transplant.
Bone Marrow transplantation or Hematopoietic stem cell transplantation is a life saving procedure in a number of diseases,hematological and non hematological, which fail alternative medical management or have no other treatment options. It has transformed the lives of thousands of patients and their families around the world battling with fatal or debilitating diseases.There are many unique aspects of bone marrow transplantation which makes it very different from solid organ transplants. There is an enormous amount of research going on in this field both at clinical and basic science levels.With the rapidly changing world and field of transplantation, there is a need for an authoritative and up to date resource for transplant professionals. This book titled Contemporary Bone Marrow Transplantation aims to be a reference text comprehensively covering various facets of hematopoietic stem cell transplants with latest insights about the technique and basic science behind it . The book is the product of collective effort of transplant professionals round the world, and will reflect their experience as well as the current standard of care practices in Stem cell transplantation.The book will be divided into different sections focusing on the basic science of bone marrow transplant, the technical aspects of the procedure itself and the supportive care of transplant patients.There will also be a section each on epidemiology, upcoming trends and also case studies , which will discuss real case scenarios from the experience of the authors, to illustrate the practical challenges in managing bone marrow transplant recipients.
This work has broad applications in clinical medicine, ranging from prevention and treatment of organ and bone marrow transplant rejection, management of various autoimmune disorders (for example, rheumatoid arthritis), skin disease and asthma. Whereas traditionally only a small repertoire of immunosuppressive agents was available for clinical use, recent discoveries have significantly increased the number of approved agents, resulting in numerous trials to further evaluate their potential. There is also considerable interest in the potential of cell-based therapies (particularly hematopoietic stem and dendritic cell therapy) of allo- and autoimmunity. Important recent advances in the immunotherapy of allergic diseases are also covered in this book. This volume is intended both for practising physicians and surgeons and for biomedical scientists at the graduate/postdoctoral levels, and is designed to provide the theory behind these various approaches to immunosuppression, and to provide state-of-the-art reviews of current developments in each area.
Produced in association with the American Society of Transplantation, this new edition is full of practical advice for the next generation of transplant professionals. In addition to 5 organ-specific chapters: kidney, pancreas, heart, lung and liver, the book includes essential information on: immunobiology pharmacology donor management infectious complications pediatric transplantation general principles of patient management Fully updated and redesigned to make it even more user-friendly, the book now contains clinical vignettes, key point boxes, and self-assessment multiple choice questions in each chapter. Primer on Transplantation, Third Edition is an invaluable resource for all health professionals in the transplant team including trainees, residents, fellows, physicians, surgeons, nurses and transplant co-ordinators. Purchasing this book entitles you to access to the companion website: www.astprimer.com The website includes: Interactive Multiple-Choice Questions for each chapter Figures from the book as Powerpoints for downloading All chapters online
THE authoritative guide for clinical laboratory immunology For over 40 years the Manual of Molecular and Clinical Laboratory Immunology has served as the premier guide for the clinical immunology laboratory. From basic serology testing to the present wide range of molecular analyses, the Manual has reflected the exponential growth in the field of immunology over the past decades. This eighth edition reflects the latest advances and developments in the diagnosis and treatment of patients with infectious and immune-mediated disorders. The Manual features detailed descriptions of general and specific methodologies, placing special focus on the interpretation of laboratory findings, and covers the immunology of infectious diseases, including specific pathogens, as well as the full range of autoimmune and immunodeficiency diseases, cancer, and transplantation. Written to guide the laboratory director, the Manual will also appeal to other laboratory scientists, especially those working in clinical immunology laboratories, and pathologists. It is also a useful reference for physicians, mid-level providers, medical students, and allied health students with an interest in the role that immunology plays in the clinical laboratory.